From Wikipedia, the free encyclopedia
Chemical compound
Ralaniten acetate (developmental code name EPI-506) is a first-in-class
antiandrogen that targets the
N-terminal domain (NTD) of the
androgen receptor (AR) developed by ESSA Pharmaceuticals and was under investigation for the treatment of
prostate cancer.
[1]
[2] This
mechanism of action is believed to allow the drug to block signaling from the AR and its
splice variants.
[3]
[4] EPI-506 is a
derivative of
bisphenol A
[5] and a
prodrug of
ralaniten (EPI-002), one of the four
stereoisomers of
EPI-001, and was developed as a successor of EPI-001.
[6] The drug reached
phase I/
II prior to the discontinuation of its development.
[1] It showed signs of efficacy in the form of
prostatic specific antigen (PSA) decreases (4–29%) predominantly at higher doses (≥1,280 mg) in some patients but also caused
side effects and was discontinued by its developer in favor of next-generation AR NTD inhibitors with improved
potency and
tolerability.
[7]
See also
References
- ^
a
b
"Ralaniten acetate - ESSA Pharma". AdisInsight. Springer Nature Switzerland AG.
-
^ Martinez-Ariza G, Hulme C (2015). "Recent advances in allosteric androgen receptor inhibitors for the potential treatment of castration-resistant prostate cancer". Pharmaceutical Patent Analyst. 4 (5): 387–402.
doi:
10.4155/ppa.15.20.
PMID
26389532.
-
^
"A phase 1/2 open-label study of safety and antitumor activity of EPI-506, a novel AR N-terminal domain inhibitor, in men with metastatic castration-resistant prostate cancer (mCRPC) with progression after enzalutamide or abiraterone". Journal of Clinical Oncology.
ISSN
0732-183X. Archived from
the original on 2016-03-06. Retrieved 2016-02-27.
-
^ Silberstein JL, Taylor MN, Antonarakis ES (April 2016).
"Novel Insights into Molecular Indicators of Response and Resistance to Modern Androgen-Axis Therapies in Prostate Cancer". Current Urology Reports. 17 (4): 29.
doi:
10.1007/s11934-016-0584-4.
PMC
4888068.
PMID
26902623.
-
^ Monaghan AE, McEwan IJ (2016).
"A sting in the tail: the N-terminal domain of the androgen receptor as a drug target". Asian Journal of Andrology. 18 (5): 687–94.
doi:
10.4103/1008-682X.181081.
PMC
5000789.
PMID
27212126.
-
^ Myung JK, Banuelos CA, Fernandez JG, Mawji NR, Wang J, Tien AH, et al. (July 2013).
"An androgen receptor N-terminal domain antagonist for treating prostate cancer". The Journal of Clinical Investigation. 123 (7): 2948–60.
doi:
10.1172/JCI66398.
PMC
3696543.
PMID
23722902.
-
^
"ESSA Pharma Announces Results from the Phase 1 Clinical Trial of EPI-506 for Treatment of mCRPC and Updates Clinical and Strategic Plans" (Press release). ESSA Pharma.
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